Abstract Details

Title Safety and Efficacy of Frexalimab in Relapsing Multiple Sclerosis: 48-week Results from the Phase 2 Open-label Extension

Topic Multiple Sclerosis

Presentation(s) S31 - Multiple Sclerosis: Therapeutics and Clinical Decision Making (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Objective

To report safety and efficacy at Week (W) 48 in the open-label extension (OLE) of the phase 2 trial (NCT04879628) of frexalimab in participants with relapsing multiple sclerosis (RMS).

Background

Frexalimab is a second-generation anti-CD40L monoclonal antibody that blocks the costimulatory CD40/CD40L pathway, which is important for activation and function of adaptive and innate immunity. In the 12-week double-blind period (DBP), frexalimab demonstrated safety and efficacy with the high-dose treatment showing an 89% reduction (vs placebo) in new gadolinium-enhancing (Gd+) T1-lesions. Over 24 weeks in the OLE, frexalimab was well-tolerated, and the number of lesions further decreased.

Design/Methods

In the DBP, participants were randomized to frexalimab_high(N=52), frexalimab_low (N=51), or matching placebo arms (placebo_high, N=12; placebo_low, N=14). At W12, participants receiving placebos switched to respective frexalimab arms and entered the OLE. Key assessments during the OLE included safety and efficacy (number of Gd+ T1-lesions and new/enlarging T2-lesions).

Results

125/129 (97%) participants completed the DBP and entered the OLE; 112 (87%) remained in the study at W48 cut-off. At W48, the number of Gd+ T1-lesions (mean [SD]) remained low in participants who continued receiving frexalimab and in those who switched from placebo to frexalimab at W12 (frexalimab_high: 0.0 [0.2]; frexalimab_low: 0.2 [0.5]; placebo_high/frexalimab_high: 0.2 [0.6]; placebo_low/frexalimab_low: 0.1 [0.3]). Furthermore, 96% participants in frexalimab_high, 87% in frexalimab_low, 90% in placebo_high/frexalimab_high, and 92% in placebo_low/frexalimab_low arms were free of Gd+ T1-lesions at W48. New/enlarging T2-lesion counts and T2-lesion volume change remained low with frexalimab_highthrough W48, and lymphocyte counts were stable over 48 weeks.Overall, frexalimab treatment was well-tolerated through W48; the most common adverse events included nasopharyngitis, headache, and COVID-19.

Conclusions

Frexalimab continued to show favorable safety and efficacy in RMS participants through W48. These data support its further development as a potential high-efficacy, non-lymphocyte-depleting treatment option in MS.

Authors/Disclosures
Patrick Vermersch (CHR de Lille) PRESENTER	Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AB Science. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS-Celgene. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ad Scientiam. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for La revue des microbiotes. The institution of Patrick Vermersch has received research support from Roche. The institution of Patrick Vermersch has received research support from Sanofi.
Gavin Giovannoni, MD (QMUL)	Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche-Genentech. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astoria Biologica. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape.
Cristina Granziera, MD, PhD (Basel University Hospital)	The institution of Prof. Granziera has received research support from Novartis. The institution of Prof. Granziera has received research support from Hoffmann La Roche. The institution of Prof. Granziera has received research support from Genzyme Sanofi. The institution of Prof. Granziera has received research support from Biogen.
Yang Mao-Draayer, MD (University of Michigan, Department of Neurology)	Dr. Mao-Draayer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen Idec. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme-Sanofi. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme-Sanofi. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizone. Dr. Mao-Draayer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen Idec. The institution of Dr. Mao-Draayer has received research support from NIH .
Gary R. Cutter, PhD (University of Alabama At Birmingham)	Dr. Cutter has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for onsulting or Advisory Boards: Alexion, Antisense Therapeutics/Percheron, Avotres, Biogen, Clene Nanomedicine, Clinical Trial Solutions LLC, Endra Life Sciences, Cognito Therapeutics, Genzyme, Genentech, Immunic, Klein-Buendel Incorporated, Kyverna Therapeutics, Inc. , Linical, Merck/Serono, Noema, Neurogenesis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Revelstone Consulting, Roche, SAB Biotherapeutics, Sapience Therapeutics, Scott&Scott LLP, Tenmile.. Dr. Cutter has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Data and Safety Monitoring Boards: Applied Therapeutics, AI therapeutics, AMO Pharma, Argenx, Astra-Zeneca, Avexis Pharmaceuticals, Bristol Meyers Squibb, CSL Behring, Cynata Therapeutics, DiamedicaTherapeutics, Horizon Pharmaceuticals, Immunic, Inhibrix, Karuna Therapeutics, Kezar Life Sciences, Medtronic, Merck, Meiji Seika Pharma, Mitsubishi Tanabe Pharma Holdings, Prothena Biosciences, Novartis, Pipeline Therapeutics (Contineum), Regeneron, Sanofi-Aventis, Teva Pharmaceuticals, United BioSource LLC, University of Texas Southwestern.. Dr. Cutter has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JASN.
Oleksandr Kalbus (Dnipro State Medical Academy)	Oleksandr Kalbus has nothing to disclose.
Ivan Staikov	Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Sanofi. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ewopharma-Biogen. Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Shire. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gedeon-Richter. Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Teva. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boehringer Ingelheim. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Polpharma. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Penumbra. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Adapt. Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Merck. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerot Lannach. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medochemie. Ivan Staikov has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Ivan Staikov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nobel Pharma.
Michal Dufek, PhD	Dr. Dufek has nothing to disclose.
Stephane Saubadu, MD	Dr. Saubadu has received personal compensation for serving as an employee of Sanofi. Dr. Saubadu has stock in Sanofi.
Raphael Bejuit (SANOFI CHILLY MAZARIN (34000))	No disclosure on file
Biljana Djukic (Sanofi)	Miss Djukic has received personal compensation for serving as an employee of Sanofi.
Philippe Truffinet, MD (Sanofi)	Dr. Truffinet has received personal compensation for serving as an employee of Sanofi.
Erik Wallstroem, MD, PhD (Sanofi)	Dr. Wallstroem has received personal compensation for serving as an employee of Sanofi. Dr. Wallstroem has stock in Sanofi. Dr. Wallstroem has received intellectual property interests from a discovery or technology relating to health care.

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